Prostate stem cell antigen (PSCA) a cell surface glycoprotein expressed in normal human prostate and bladder is over-expressed in prostate cancers (40% of primary tumors and 60-100% of lymph node and bone marrow metastases). It is also highly expressed in transitional carcinomas of the bladder and pancreatic carcinoma. 1G8, an anti-PSCA mouse monoclonal antibody specific for PSCA demonstrated anti-tumor targeting activity in vivo (Gu Z, et al. Cancer Res. 2005; 65:9495). This antibody was humanized by grafting on a human framework (Trastuzumab) and named 2B3 (Olafsen T, et al. J. Immunotherapy 2007; 30:396).
The invention addresses the need for agents that have appropriate pharmacodynamic properties to target and image tumors that express PSCA. There is a tremendous need in the field for effective agents to image cancers with sensitivity and specificity, particularly early stage tumors or ones with early metastasis not imageable by traditional means. As PSCA is highly expressed by most prostate, bladder and pancreatic tumors, it is an important target in the detection, diagnosis, prognosis, and treatment of these cancers. The current invention describes an innovative constructs with optimal characteristics for tumor imaging and targeting. They may also be used for tumor targeting of gene therapy, radioactivity therapy, and may have therapeutic utility by themselves.